Thioketones containing a cycloalkyl group



Patented Oct. 21, 1947 u-NirEo STATES PATENT osmos- THIOKETONESCONTAINING-.718 CYCLO- ALKYL GROUP Grafton H. Keyes, Rochester, N. Y.,assignor. to Eastman Kodak CompanyyRochester, N; -Y. a corporation ofNew Jersey N Drawing. Application June- 1, 1945', Serial No. 597,149

11 Claims.

This invention relates tothioketones containing. a tcycloalkyl .groupand-to a: processfor preparing the. same. This applicationl is a continuation-in-part ofmy copending applicationSerial No.. 478,007, filed Marchl, 1943, and-a continuation-in-part of the copending application .ofLeslie G. SL Brooker and Grafton H.-Keyes Serial No. 515,978; filedDecember 28,1943} The thioketones of myinvention can -.be represented bythe following general formula:

/Z\ Il 1 R-rf b=o-H-o=s whereinR represents an alkyl. or aryl group, R1represents a cy loalkyl group containing from 3: to fifcarbon atoms inthe ring and Z represents the non-metallic atoms necessary to complete ahet'erocyclic nucleus selected from those consisting of those vof thebenzothiazole series, those of the benzoselenazole series, those of theu-naphthothiazole' series, those of the p naphthothiazole' series, thoseof the a-naphthoselenazole series and those of the. B-naphthoselenazoleseries.

The thioketones of my invention, especially those whereinR represents analkyl groupcont'ainingfrom l to 4' carbon atoms, can be condensed' withalkyl salts to give v alkylmercapto' compounds of the following generalformula:

wherein R, R1 and Z have the values given above and R2 represents analkyl group and X represents an anion. The alkylmercapt'ocompounds canbe condensed; as shown'in the aforesaid Brooker and Keyes applicationSerial No. 515,978, with cyclammoniumequaternary salts containing areactive methylgroup to give mesocycloalkyl carbocyanine dyes, orwithheterocyclic compounds containing an intracyclicketomethylene amideis advantageously carried out i'n-the presence of a' diluent; suchfa's alower aliphaticalcohol, e; g. methyl; ethyl'or isopropyl' alcohol: Heataccelerates the condensation.

The .5-cycloalkyl p=halogenovinylcompounds can" be prepared bycondensing aketone derivative of aheterocyclic nitrogen base ofthefQ11OW' in'g general formula:

,z R1; R1\'I' o=on=o wherein R, R]; andZ have thevalues g-iven abovewith-a phosphorus oxychloride; The condensation is advantageously butnot necessarily effected. in the presence of a diluent.Thereaction-takesplace veryreadily, so'that, in somecasespit i'sadvantageous to chill the-reactionmixtura Ben-- zene, toluene,chloroform or carbontetra'eh-loride are suitable .diluentswithswhichato.efiect the condensation. 'Phosphorusjoxychloride (POCls) isadvantageously employed.

The ketone derivatives of. the, heterocyclic nitrogen bases can beprepared by condensing a cyclammonium quaternary salt of the followinggeneral formula:

wherein R, 'Xand- Z havethe Valujesrset forth above with a cycloalkane.carboxylic acidichlo' ride,- in the presence ofan acid-binding .agent;

Ordinarily; to effect the; condensation; the; quaternarys'alt isadvantageously"suspendedinacold,

dry pyridine, the suspensionv cooled. to Y.-l0,to- +10 C. and: the.cycloalkane carboxylicxhalide' added graduall'y tozthe chilled:suspension with. agitation. Other: tertiaryiaminese; g. tria1lylaminesor dialkylanilines can be employedlas the acid-binding agent.

The following examples will serve; torillustrate my'new.thioketonesandithe manner of obtaining the same.

Example 1.2-cyclopropylthioformylmethylene- S-ethylbenzothiazoline 15.31g. (1- 11101;) of 2-cyclopropylformylmethyl--one-3-ethylbenzothiazolinewas dissolved-in 50 cc. of dry benzene. 14 .2g. (1*.5 molI) of-phosphorus oxychloride was added and the mixture wellstirred. After a few minutes the 2-(p-chlorop-cyclopropylvinyl)benzothiazole ethochloride which had formed was precipitated on additionof 100 cc. of ether. This was collected on a filter and added to asolution of 4.7 g. (1 mol.) of thioacetamide in 25 cc. of ethyl alcohol.The mixture was heated under reflux for minutes. The thioketoneseparated on chilling and was collected on filter, washed with water anddried. It was purified by two successive recrystallizations from methylalcohol and obtained as yellow crystals. Melting point 123-125 C.

The 2-cyclopropylformylmethylene 3 ethylbenzothiazoline employed abovewas prepared as follows:

30 g. (1 mol.) of 2-methylbenzothiazole ethop-toluene-sulfonate wassuspended in 50 cc. of pyridine and the mixture chilled by means of afreezing mixture of ice and acetone. 9.1 g. (1 mol.) of cyclopropanecarboxylic acid chloride was added slowly with good stirring. Thismixture was allowed to stand in the cold for about 15 minutes. It wasthen removed from the freezing mixture and allowed to come slowly toroom temperature and finally was heated to the temperature of a steambath. The ketone separated as a sticky mass when the pyridine solutionwas poured into 500 cc. of cold water. After collecting on a filter, itwas purified by recrystallizing from ligroin.

In a similar manner, 2-cyclopropylthioformylmethylene 3methylbenzothiazoline was prepared as yellow-orange needles melting at171- 172 C. dec. Similarly5-chloro-2-cyclopropylthioformylmethylene-3-ethylbenzothiazoline wasprepared as opaque yellow crystals melting at 189 to 191 C.

Example 2.2-cyclopropylthioformylmethylene- 1-ethyZ-p-napththothiazoline 10.4 g. (1 mol.) of2-cyclopropylformylmethylene-1-ethyl-,B-naphthothiazoline was suspendedin 35 cc. of dry benzene. 8.1 g. (1.5 mol.) of phosphorus oxychloridewas added and the mixture stirred at room temperature for about minutes.The 2-(13-chloro s-cyclopropylvinyl)- fi-naphthothiazole ethochlorideformed by the above reaction separated on chilling and was collected ona filter and washed with ether. It was added to a solution of 2.6 g. (1mol.) thioacetamide in 35 cc. of absolute ethyl alcohol and the mixturerefluxed for 5 minutes. Thioketone separated on chilling and wascollected on filter, washed with water and dried. It was purified byrepeated recrystallization from methyl alcohol and obtained as amberflakes. Melting point 179-181 C. dec.

The 2-cyclopropylformylmethylene-l-ethyl-B- naphthothiazoline employedabove was prepared as follows:

39.9 g. (1 mol.) of 2-methyl-,3-naphthothiazole etho-p-toluenesulfonatewas dissolved in 50 cc, of pyridine and chilled in freezing mixture oficeacetone. 10.4 g. (1 mol.) cyclopropane carboxylic acid chloride wasadded slowly with good stirring. The mixture was allowed to stand 5minutes in '4 the cold, then allowed to come to room temperature andfinally heated to the temperature of a steam bath. The ketone separatedas a sticky mass when poured into a large volume of cold water. It waspurified by recrystallization from ligroin.

In a similar manner 2-cyclopropylthioformylmethylene-l-methyl ,6naphthothiazoline was prepared as yellow crystals melting at 175 to 177C. dec.

Example 3.-2-cyclopropylthioformylmethylene- 3-ethylbenzoselenazolineC=CH-C=S CH 4 ol om 17 g. of 2 cyclopropylformylmethylene 3ethylbenzoselenazoline was suspended in cc. of dry benzene. 13.4 g. (1.5mol.) of phosphorus oxychloride was added with stirring. After about 10minutes the chloro intermediate separated and was collected on filterand washed with ether. It was then added to a solution of 4.4 g. (1mol.) thioacetamide dissolved in 50 cc. of absolute ethyl alcohol andthe mixture refluxed for 5 minutes. The thioketone separated onchilling. It was collected on filter, washed with water andrecrystallized from methyl alcohol. It was obtained as yellow crystals.Melting point 111-113 C.

The 2-cyclopropylformylmethylene-3-ethylbenzoselenazoline employed wasprepared as follows: 34.2 g. (1 mol.) of 2-methylbenzoselenazoleethiodide was suspended in 75 cc. of pyridine and the mixture chilled ina freezing mixture of ice-acetone. 10.4 g. (1 mol.)cyclopropanecarboxylic acid chloride was added slowly with goodstirring. The mixture was stirred in the cold for a 15-minute period. Itwas removed from the freezing mixture and heated gradually totemperature of the steam bath. 0n pouring into a large volume of coldwater, the ketone separated. It was collected on filter and washed withwater. i It was further purified by recrystallization from ligroin.

Example 4.5chloro-Z-cyclopropylthioformylmethylene-3ethylbenzothiazoline 16.7 g. (1mol.) of 5-chloro-2-cyclopropylformylmethylene-3-ethylbenzothiazolinewas dissolved in 50 cc. of dry benzene, 13.8 g. (1 mol.) of phosphorusoxychloride was added with stir ring. After about 10 minutes theZ-(B-chlorofl-cyclopropylvinyl)-5-chlorobenzothiazole ethochloride whichhad formed separated and was collected on filter and washed with ether.This was added to a solution of 4.5 g. (1 mol.) of thioacetamide in 30cc. of absolute ethyl alcohol and the mixture refluxed for 5 minutes.Thioketone separated on chilling and was collected on filter, washedwith water and dried. It was purified by repeated recrystallizationsfrom methyl alcohol and obtained as opaque yellow crystals. Meltingpoint 189-191 C. dec.

The. 5 chloro-2-cyclopropylformylmethylene- 3-ethylbenzothiazolineemployed above was prepared as follows:

3.8.3 g. (1 mol.) of -chloro-2-methylbenzothiazole etho-p-toluenesulfonate was suspended in 50 cc. of pyridine and chilled in a freezingmixture of ice-water. 10.4 g. (1 mol) of cyclopropane carboxylic acidchloride was added slowly with good stirring. The mixture was allowed tostand 15 minutes in the cold, then allowed to come to room temperatureand finally heated a few minutes on a steam bath. Ketone separated onpouring into a large volume of cold water. It was collected On a filter,washed with water and dried. It was further purified byrecrystallization from ligroin.

In a similar manner,5-chloro-2-cyclobutylthioformylmethylene-3-ethylbenzothiazoline wasprepared as yellow crystals melting at 150-152 C.

Example 5.2-cyclohexylthioformylmethylene-3- et'hylbenzothiazolme 45 g.(1 mol.) of 2-cyclohexylformylmethylene- B-ethylbenzothiazoline wassuspended in 100 cc. of dry benzene. 36 g. (1.5 mol.) of phosphorusoxychloride was added and the mixture well stirred. After a few minutesthe Z-(fi-chloro- ,B-cyclohexylvinyl) benzothiazole ethochloride whichhad formed was precipitated on addition of 200 cc. of ether. Thisproduct was collected on a filter and washed with acetone. It was thenadded to a solution of 11.7 g. (1 mol.) of thicacetamide in 100 cc. ofethyl alcohol. This mixture was heated under reflux for five minutes.The thioketone separated on chilling and was collected on filter, washedwith water and purified by recrystallization from methyl alcohol.Melting point 146-148 C.

The 2-cyclohe-xylformylmethylene-3-ethylbenzothiazoline used above wasprepared as follows:

69.8 g. (1 mol.) of Z-methylbenzothiazole ethop-toluene-sulfonate wassuspended in 200 cc. of pyridine and the mixture chilled by means of afreezing mixture of ice and acetone. 36.4 g. (1.25 mol.) ofhexahydrobenzoyl chloride was added slowly with good mechanicalstirring. This mixture was allowed to stand in the cold for a 15- minuteperiod. t was then removed from the freezing mixture and stood at roomtemperature for 15 minutes; then, after heating to tempera ture of asteam bath, as much as possible of the pyridine was removed bydistillation under reduced pressure. The residue was poured out into iceand water. The product separated as a crystalline solid and wascollected on a filter and washed with water. After recrystallizationfrom methyl alcohol, it was pure enough for use.

In a similar manner5-chloro-2-cyclohexylthioformylmethylene-IB-ethylbenzothiazoline wasprepared as orange crystals melting at 151-153 C. .Also in a similarmanner, Z-cyclohexylthioformylmethylene-l-ethyl B naphthothiazoline wasprepared as yellow crystals melting at 191-193 C. Likewise, in a similarmanner, Z-cyclohexylthioformylmethylene- 3 -ethylbenzoselenazoline wasprepared as orange-yellow crystals melting at 147-149 C.

Alternatively, I have found that the thioketones of my invention can beprepared by condensing a cyclammonium quaternary salt of the followinggeneral formula:

wherein'R, X and Z have the values set forth above with an ester of adithiocycloalkane carboxylic acid. Advantageously the condensation iseffected in the presence of a basic condensing agent,'i. e. anacid-binding agent. As basic condensing agents, organic tertiary aminesare advantageously employed, e. g. trialkylamines, piperidine, orN-methylpiperidine.

The following example will serve to illustrate this alternative processfor obtainin my new thioketones:

Example 6.2-cycloherylthioformylmethylene-3 ethylbenzothz'azoline '14 g.(1 mol.) of Z-methylbenzothiazole etho-ptoluenesulfonate, 7 g. (1 mol.)of methyl ester of dithiocyclohexane carboxylic acid, 40 cc. of absoluteethyl alcohol and 4 g. (1 mol.) of triethylamine were heated, underreflux, for 30 minutes. The thioketone was precipitated from thereaction mixture by the addition of 2 liters of cold water. The crudethioketone was extracted several times with hot ligroin. The thioketonewhich separated from the combined ligroin extracts upon chilling, wererecrystallized twice from ligroin and then once from methyl alcohols.The thioketone was obtained as orange crystals, melting at 146 to 148 C.

In a manner similar to that illustrated in the foregoing examples, theother thioketones within the purview of my invention can be prepared.Thus 2-cyclopropylthioformylmethylene 3 nbutylbenzothiazoline can beprepared from 2-(13- chloro-,B-cyclopropylvinyl) -benzothiazolen-butochloride and thioacetamide;2-cyclobutylthioformylmethylene-3-ethylbenzothiazoline can be preparedfrom 2-(c-chloro-c-cyclobutylvinyl)- benzothiazole ethochloride andthioacetann'de; 2- cyclopentylthioformylmethylene- 3-methylbenzothiazoline can be prepared from 2-(13-ChlOrO-B- cyclopentylvinyl)-benzothiazo1e methochloride; 2 cyclopropylthioformylmethylene 1ethyl-,8- naphthoselenazoline can be prepared from 2-(5-chloro-,6-cyclopropylvinyl) B -naphthoselenazole ethochloride;2-cyclopropylthioformylmethylene- 3-phenylbenzothiazoline can beprepared from 2- ,B chloro ,8 cyclopropylvinyl) benzothiazolephenochloride and 2-cyclopropylthioformylmethylene-3-}8-ethoxyethylbenzothiazoline can be prepared from2-(,8-chloro-fl-cyclopropylvinyl) -benzothiazole-fl-ethoxyethochloride.

Any of the thioketones of my invention can be converted to alkylmercaptocompounds by heating (e. g. at to 150 C.) with alkyl salts, especiallyalkyl salts containing from 1 to 4 carbon atoms, e. g.ethyl-p-toluenesulfonate, methyl-ptoluenesulfonate, dimethylsulfate,n-butyl chloride, n-propyl bromide, isopropyl iodide,

ethoxyethyl bromide or p-hydroxyethyl bromide. Benzyl iodide can also beemployed. The anion of these alkylmercapto compounds can be changed andless soluble alkylmercapto compounds formed, e. g. the perchlorates canbe formed by treating the alkylmercapto compounds in chloride, bromideor p-toluenesulfonate form with an aqueous solution of an alkali metalperchlorate, e. g. sodium perchlorate.

2-cyclopropylthioformylmethylene-3-ethy1benzothiazoline, when heated ona steam bath with an equimolecular proportion ofmethyl-p-toluenesulfonate for 30 minutes, yielded solidZ-(fl-cyclopropyl ,9 methylmercaptovinyl) benzothiazolemetho-p-toluenesulfonate.

2-cyclopropylthioformylmethylene- 1 -ethyl naphthothiazoline, whenheated on a, steam bath with an equimolecular proportion ofmethyl-p-toluenesulfonate for 30 minutes, yielded solid 2-(5-cyclopropyl-p-methylmercaptovinyl) -p-naphthothiazolemetho-p-toluenesulfonate.

5-chloro- 2- cyclopropylthioformylmethylene-3- ethylbenzothiazoline,when heated in an oil bath at 130 C. with an equimolecular proportion ofmethyl-p-toluenesulfonate for 30 minutes, yielded solid 5-chloro-2-(3-cyclopropyl-p-methylmercaptovinyl) -benzothiazolemetho-p-toluenesulfonate.

2-cyclopropylthioformylmethylene-3-ethylbenzoselenazoline, when heatedon a steam bath with an equimolecular proportion ofmethyl-p-toluenesulfonate for one hour yielded solid2-(p-cyclopropylp-methylcercaptovinyl) benzoselenazolemetho-p-toluenesulfonate.

2-cyclobutylthioformylmethylene- 3 -ethylbenzothiazoline, when heated ona steam bath for 30 minutes with an equimolecular proportion ofmethyl-p-toluenesulfonate, yielded solid 2- (p-cyclobutyl-p-methylmercaptovinyl) benzothiazole metho-p-toluenesulfonate.

2-cyclohexylthioformylmethylene- 3 -ethylbenzothiazoline, when heated ona steam bath for 30 minutes with an equimolecular proportion ofmethyl-p-toluenesulfonate, yielded solidZ-(p-cyclohexyl-fl-methylmercaptovinyl) benzothiazolemetho-p-toluenesulfonate.

What I claim as my invention and desire to secure by Letters Patent ofthe United'States is:

l. A compound selected from the group consisting of the compounds whichare represented wherein R represents a member selected from the groupconsisting of alkyl and aryl groups, R1 represents a cycloalkyl groupcontaining from 3 to 6 carbon atoms in the ring, R2 represents an alkylgroup, X represents an anion, and Z represents the non-metallic atomsnecessary to complete a heterocyclic nucleus selected from the groupconsisting of those of the benzothiazole series, those of thebenzoselenazole series, those of the a-naphthothiazole series, those ofthe fi-naphthothiazole series, those of the a-naphthoselenazole seriesand those of the ,B-naphthoselenazole series.

2. The thioketones of the following general formula:

wherein R represents a member selected from the group consisting ofalkyl groups and aryl groups, R1 represents a cycloalkyl groupcontaining from 3 to 6 carbon atoms in the ring and Z represents thenon-metallic atoms necessary to complete a heterocyclic nucleus selectedfrom the group consisting of those of the benzothiazole series, those ofthe benzoselenazole series, those of the a-naphthothiazole series, thoseof the fi-naphthothiazole series, those of the unaphthoselenazole seriesand those of the pnaphthoselenazole series.

3. The thioketones of the following general formula:

wherein R represents an alkyl group containing from 1 to 4 carbon atoms,R1 represents a cycloalkyl group containing from 3 to 6 carbon atoms,and Z represents the non-metallic atoms necessary to complete aheterocyclic nucleus of the benzothiazole series.

4. The thioketone of the following formula:

5. The thioketones of the following general formula:

.2, R-N c=cH-c=s E 0H=0H,

wherein R represents an alkyl group of from 1 to 4 carbon atoms and Zrepresents the nonmetallic atoms necessary to complete a heterocyclicnucleus of the benzothiazole series.

6. The thioketones of the following general formula:

,z. R1 RI T---b=OH-l=8 wherein R represents an alkyl group containingfrom 1 to 4 carbon atoms, R1 represents a cycloalkyl group containingfrom 3 to 6 carbon atoms and Z represents the non-metallic atomsnecessary to complete a heterocyclic nucleus of the benzoselenazoleseries.

7. The thioketones of the following general formula:

lzs R1- -o=on-c=s wherein R represents an alkyl group containing from 1to 4 carbon atoms and Z represents the non-metallic atoms necessary tocomplete a heterocyclic nucleus of the benzoselenazole series.

8. The thioketone of the following general formula:

9 9. The thioketones of the following general formula:

,z ll! R-1 Io=oH-o=s wherein R represents an alkyl group containing from1 to 4 carbon atoms, R1 represents a cycloalkyl group containing from 3to 6 carbon atoms and Z represents the non-metallic atoms necessary tocomplete a heterocyclic nucleus of the B-naphthothiazole series.

10. The thioketones of the following general formula:

,2. R-N' -o=011o=s f5 OH2OH;

wherein R represents an alkyl group containing from 1 to 4 carbon atomsand Z represents the 2 non-metallic atoms necessary to complete aheterocyclic nucleus of the ,s-naphthothiazole series.

11. The thioketone of the following formula:

OH N The following references are of record in the 15 file of thispatent:

UNITED STATES PATIL! NIS

